Differential interactions of the catalytic subunits of adenylyl cyclase with forskolin analogs.

ABSTRACT: The diterpene forskolin (FS) binds to, and activates, mammalian membranous adenylyl cyclase (AC) isoforms I-VIII. Diterpenes without C(1)-OH group do not activate ACs. The C(1)-OH group forms a hydrogen bond with the backbone oxygen of Val506 of the C1 catalytic subunit of AC (isoform V numbering). To better understand the mechanism of AC activation we examined the interactions of FS and eight FS analogs with purified catalytic AC subunits C1 (AC V) and C2 (AC II) by fluorescence spectroscopy, using 2',3'-O-(N-methylanthraniloyl)-guanosine 5'-triphosphate (MANT-GTP) as fluorescent reporter probe, and by enzymatic activity. FS analogs induced C1/C2 assembly as assessed by fluorescence resonance energy transfer from Trp1020 of C2 to MANT-GTP and by increased direct MANT-GTP fluorescence in t

SUBMITTER: Pinto C 

PROVIDER: S-EPMC2692545 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature